Panchuk R. Role of cytokines in mechanisms of endogenous intoxication, caused by tumor growth and under action of anticancer drugs (on the model of murine NK/Ly lymphoma)

Object - pro-inflammatory cytokines and proteins, involved in regulation of cell proliferation and apoptosis, in tumor cells during NK/Ly lymphoma development. The aim of the study is to investigate molecular processes, which take place during NK/Ly lymphoma growth in mice, and to identify main factors, which affect this pathological condition. We have estimated functional status of lymphoma cells at early and terminal stages of NK/Ly lymphoma development, as well as pathophysiological changes in the organism of tumor-bearing animals. Expression of pro-inflammatory cytokines (IL-1a, IL-1b, IL-6, IFN-g, VEGF, TNFa, TNFb) by NK/Ly lymphoma cells was measured by levels of their mRNA in tumor cells and protein concentration in ascitic fluid of tumor-bearing animals. We also analyzed changes in production of protease inhibitors during NK/Ly lymphoma development using protein electrophoresis and MALDI-TOF mass-spectrometry. Using Western-blot assay with specific antibodies to proteins, involved in regulation of cell proliferation, cell cycle and apoptosis, we studied signaling pathways, which are activated in tumor cells during NK/Ly lymphoma development. Changes in cytokines expression and in signaling systems in tumor cells during treatment of tumor-bearing animals with antitumor drugs with different mechanisms of cytotoxic activity were also measured. For this ELISA and Western-blot assays were used. Area of use - cell biology, pharmacology.